The advantages of long-acting or sustained release products are well-known to the art and are of extreme importance in the pharmaceutical field. Through the use of such products, medication can be administered for uniform and continuous release over a prolonged period of time to achieve a stable and desired blood level of the active ingredient without requiring frequent administration of the medicament. Numerous objectives must be considered in the preparation of an effective controlled release pharmaceutical formulation. Among such objectives are obtaining uniform and constant dissolution and efficacy for a prolonged period of time, ease of preparation, acceptability of taste and adaptability for use with a wide variety of therapeutic agents.
Previously developed long-acting formulations are only capable of satisfying some of these objectives. For example, some conventional sustained release therapeutic compositions use a base material comprised of a copolymer of cellulose material in admixture with an active therapeutic ingredient. The copolymer used is difficult to manufacture and has a moisture content which renders it unacceptable for use with hygroscopic materials. The moisture content of the heretofore known copolymer base materials, for example, results in the production of salicylic acid when aspirin contacts the copolymer. The salicylic acid so produced exhibits undesirable taste and odor and is not permitted to be marketed in this form. Therefore, it is desirable to develop a dry pharmaceutical carrier which can be effectively used with hygroscopic active therapeutic agents such as aspirin. From the standpoint of maximizing the effectiveness and adaptability of a carrier for use with both non-hygroscopic and hygroscopic materials, a new dry carrier composition with a minimum moisture content is especially important.
The use of cellulosic derivatives such as hydroxypropyl methylcellulose as an ingredient in pharmaceutical formulations is known. However, none of these formulations has been found to be effective in admixture with hygroscopic therapeutic agents. Thus, in U.S. Pat. No. 3,590,117 the inadequacy of hydroxypropyl methylcellulose for use in long-lasting troches used as a vehicle for administering active medicaments is disclosed. The use of high viscosity gums such as hydroxypropyl methylcellulose having a viscosity of 15,000 centipoise for a 2% aqueous solution at 20.degree. C. proved unacceptable because the troche would "flake-off" in the mouth rather than dissolve uniformly. Alternatively, troches made from low viscosity hydroxypropyl methylcellulose, while avoiding the problem of "flaking-off", produced a "gagging" effect due to the highly viscous and adhesive characteristics of the saliva produced in the mouth. Later developments, as described in U.S. Pat. No. 3,870,790, relate to mixing an active therapeutic ingredient with a copolymer of a premoisturized hydroxypropyl methylcellulose powder which could also be optionally mixed with an ethylcellulose powder. The release period of the active medicament is controlled as a function of a predetermined moisture content of the alkylated cellulose carrier powder; however, the pharmaceutical formulations containing such a moisturized copolymer could not be successfully used with hygroscopic materials.
Therefore, a need exists for a controlled long-acting dry pharmaceutical formulation which can be easily and inexpensively prepared and which has all of the desirable properties of uniform and continuous dissolution over a prolonged period of time and which can also be used with a greater variety of medicaments including those which are hygroscopic.